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Biomedical subjects

K Winkler

Publications and source records attributed to K Winkler.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

[Initial response to therapy as an important prognostic factor in acute lymphoblastic leukemia in childhood. COALL study group].

Prognostic factors to estimate the risk of relapse are crucial for risk-adapted therapy in acute lymphoblastic leukemia (ALL). In a cooperative multicenter treatment study for childhood ALL (COALL-03-85) the prognostic relevance of the bone marrow (BM) blast count at day 28 was evaluated. Treatment was adjusted to the initial risk factors; patients with high risk (white blood count (WBC) greater than or equal to 25/nl, age greater than or equal to 10 years, T- or NULL-ALL) received intensified therapy consisting of rotation of 6 non cross-resistant drug combinations with 12 different agents. After 4 weeks 289/305 (94.8%) children were in complete remission (CR); one child died of infection, and 15 (14 high-risk patients) still had more than 5% blasts in the BM. Twelve of these 15 patients were in remission after 2 to 4 weeks additional treatment. Poor responders often had a high initial WBC, age above 10 years of T- or NULL-ALL. In spite of continuation of intensive therapy all children with more than 10% blasts in the BM on day 28 suffered an early relapse except 2 who were transplanted in first remission. Event-free survival for the poor responders is 0.15 compared to 0.71 (p = 0.0001) for the good responders (median observation time 48 months). In multivariate analysis remission status on day 28 was the only significant prognostic factor in high-risk patients above one year of age; traditional risk factors as initial WBC, age above 10 years, hepatosplenomegaly, and immunological subtype were of no prognostic significance in this study. (ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Cardiomyopathy after osteosarcoma treatment: a contribution to the cardiotoxicity of adriamycin].

The frequency and severity of clinical and subclinical heart damage were studied in patients who had been treated with adriamycin (ADR) as part of the Cooperative Osteosarcoma Studies (COSS). The study charts of 785 patients from 63 participating institutions were reviewed: The overall incidence of drug-induced congestive heart failure was 2.2% (17 cases, 5 fatal). Late left ventricular function was studied in 29 tumor free survivors 81 +/- 41 month after treatment with 342 +/- 113 mg/m2 ADR. A detailed history and physical exam for signs of overt heart disease were obtained. M-mode echocardiography (ECHO, 29 cases) with evaluation of the fractional shortening rate (FS) and radionuclide ventriculography (RNV, 18 cases) with determination of the systolic ejection fraction at rest (EF) were used to screen for subclinical cardiac disease. Impaired cardiac function leading to pathological values was documented in close to one half of these patients. The frequency and severity of clinical and subclinical heart damage increased with cumulative adriamycin and time since cessation of anthracycline therapy.

Adolescent↗
PubMedDate not supplied

[Results of the treatment of non-rhabdomyosarcomatous soft tissue neoplasms within the scope of the CWS 81 study].

347 children with all types of soft tissue sarcoma (STS) have been entered between 1981 and April 1986 into the CWS-81 study. Excluding 229 patients with rhabdomyosarcoma, 118 patients with other STS were analysed in the histological subgroups, separately. 33 synovial sarcomas (SyS), 15 undifferentiated sarcomas (US) and 13 extrasceletal Ewing's sarcoma (EES) were treated with a multimodale trial including chemotherapy and radiotherapy after initial not-mutilating resection or biopsy only, Relapse-free survival rate by Kaplan-Meier was 66% in SyS, 48% in EES and 38% in US, respectively. Patients treated according to the guidelines of the CWS-protocol showed better prognosis than patients with major protocol violations or patients with recurrence when entered into the trial. In SyS only 2 of the 7 patients with recurrence developed metastases. The tumor response rate within 7-9 weeks chemotherapy exclusively given was 71% in patients with stage III and IV. Non-responding tumors to chemotherapy had bad prognosis, irrespective of histological subtype or further treatment. EES and US developed earlier recurrence and more often metastases than SyS or rhabdomyosarcomas. The administered VACA-chemotherapy seems not to be very effective in EES and US. In all other varieties of STS recurrence at the primary site assumed relatively greater importance. Chemotherapy and radiation were not administered in all patients. Fibrosarcoma (FS) was diagnosed in 13 patients. Six of these were entered in the trial at the time of local recurrence and 4 of these 6 relapsed again locally, one with metastasis concurrently.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Acute lymphoblastic leukemia in childhood: the COALL studies].

In the cooperative study COALL-80 151 children with acute lymphoblastic leukemia were treated according to the modified protocol BFM 79/81. The probability of continuous complete remission (CCR) for the total group is 74% after 6 years. In the subsequent study COALL-82 high-risk patients (initial white blood count greater than or equal to 25/nl or T-cell leukemia and acute undifferentiated leukemia) received additional high-dose methotrexate as fifth drug in the intensive phase and the combination VM-26/arabinosyl-cytosine in the reinduction phase. In all others patients (low-risk group) intermediate-dose methotrexate was substituted for the myelosuppressive agent cyclophosphamide in the intensive phase. Reinduction was no longer given in the low-risk group. In both risk groups cranial irradiation was postponed until after the intensive phase therapy. Radiotherapy was withheld for a group with minimal risk (white blood count less than 3/nl, liver/spleen less than 3 cm). The probability of CCR for the total group of 129 patients is 64% after 3.5 years. The comparative analysis between the studies COALL-82 and COALL-80 shows that low-risk patients have an equally high probability of continuous hematologic remission (91% vs. 85%) despite reduction of therapy in COALL-82. High-risk patients, however, had a significantly higher rate of bone marrow relapses; in this group the probability of continuous hematologic remission is 52% in COALL-82 vs. 73% in COALL-80. Also relapses in the central nervous system in irradiated patients were significantly more frequent in COALL-82 than in COALL-80 (12% vs. 4%) whereas the group of patients without radiotherapy has remained free of relapse. The possible influence of the modifications in therapy in study COALL-82 on the higher relapse rate is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[The COALL-85 cooperative study for risk patients with acute lymphatic leukemia: initial results].

A frequent change of non-crossresistant drug combinations might obviate the problem of multiple resistant cell lines in malignant diseases and thus increase cure rates. In a multicenter cooperative study for childhood acute lymphoblastic leukemia (ALL) 109 high-risk patients were randomized to receive 5-6 different drug combinations either in slow rotation (change of drugs every 4-6 weeks) or in rapid rotation (change of drugs every 2-3 weeks) for early intensive treatment. Both groups received the same total amount of drugs within the same period of time. 108/109 patients achieved complete remission. One child failed to enter remission and one was lost in remission due to viral infection. Patients in the rapid rotation arm required 2-3 weeks less time to complete the intensive therapy due to fewer episodes of prolonged myelosuppression. Toxic side effects and infectious complications were comparable in both groups. 9/109 patients relapsed, 6 in the bone marrow and 3 in the central nervous system. As yet none of the 31 patients with an initial white blood count of greater than or equal to 100/nl has relapsed. The probability of relapse-free survival is 88% in the rapid rotation arm and 86% in the slow rotation arm at 2 1/2 years. The results compare favourably with other protocols for high-risk patients but have still to be considered as preliminary because of the short median observation time of 18 months.

Adolescent↗
PubMedDate not supplied

[Cooperative osteosarcoma study COSS-77: results after 4 years].

71 patients with resectable osterosarcoma received chemotherapy for one year including high-dose methotrexate (18 x 200 mg/kg), adriamycin (5 x [2 x 45] mg/m2) and cyclophosphamide (6 x 1200 mg/m2). During the initial 15 weeks adriamycin was used preferentially and cytostatic agents were applied in a higher frequency than later on. 41/71 patients are continuously free of disease with a median follow up of 39 (24-54) months. The latest appearance of pulmonary metastases was observed at 28 months so far. 18/27 (67%) patients with extension of tumor lesion beyond 1/3 long bones length by x-ray examination relapsed in contrast to 12/43 (28%) patients with smaller lesions. 1 patient died from adriamycin induced cardiomyopathy. Generally therapy was well tolerated. An average of 70-80% of planned drug dosages could be realized without measurable influence of individual differences on outcome.

Adolescent↗
PubMedDate not supplied

[The Cooperative Ewing Sarcoma Study CESS 81 of the German Pediatric Oncology Society--analysis after 4 years].

In 1981 the cooperative Ewing's sarcoma study CESS 81 was initiated with initial 18-weeks-chemotherapy consisting of vincristine, actinomycin D, cyclophosphamide and adriamycin (VACA) followed by local therapy consisting of either radical surgery with complete resection of the involved bone or incomplete resection followed by radiation with 36 gy or radiotherapy only. Patients with radiation only for local therapy and extremity tumor sites are randomised for 46 gy vs 60 gy tumor dose. Following local therapy chemotherapy is continued for an additional 18 weeks. The actuarial results of 83 consecutive patients entered from 51 participating institutions from January 1, 1981, until November 15, 1984 are presented. 68/83 patients were off therapy and under observation for longer than one year following diagnosis. The longest follow-up was 41 months. On November 15, 1984, 39/68 (57%) patients were disease free. According to the site of the primary tumor patients with distal extremity lesions had a more favourable prognosis as compared to proximal extremity and central lesions. According to local therapy patients with radical surgery had a better prognosis as compared to those with resection followed by radiation and those with radiation only for local control. Analysis according to tumor volume revealed the strong interaction between tumor site, local therapy and tumor volume. According to life-table-analysis the disease free survival for patients with a tumor volume less than 100 ml was 75% after 41 months compared to 10% for patients with a tumor volume greater than or equal to 100 ml. The consequences of this analysis for a stratified treatment regimen for patients with primary Ewing's sarcoma of bone are discussed.

Adolescent↗
PubMedDate not supplied

[Results of the COSS-77 and COSS-80 studies on adjuvant chemotherapy in osteosarcoma of the extremities].

In the first study, COSS-77, 100 patients with OS were treated for 12 months according to a CT-protocol consisting of high-dose methotrexate (HD-MTX), adriblastine (ADR) and cyclophosphamide (CP). At 40 months the expected continuous disease-free survival (CDFS) rate of the 71 evaluable patients was 55%. After exclusion of local recurrences (n = 2) and fatal chemotherapy toxicities (n = 0) a reduced group of 69 patients remained and the expected CDFS rate at 40 months became 56%. In the second study, COSS-80, the MTX dose was doubled. Two groups were randomly selected, one of which received cisplatinum (CPL) and the other the triple drug combination bleomycin + CP + dactinomycin (BCD) in addition to MTX and ADR, both groups being treated for 8 months. Furthermore some randomly selected patients received fibroblaste-interferon (IF). The expected CDFS rate at 40 months of the 115 evaluable COSS-80 patients was 67%. 106 patients remained in a reduced group defined as above (4 local recurrences and 5 CT toxicities) in which the expected CDFS rate at 40 months was 73%. This is significantly better (p less than 0.05) than the results obtained from the COSS-77 group. No differences were found between the CPL and BCD arms of the COSS-80 group or between the arms receiving or not receiving IF. A significant increase in the CDFS rate for young (less than 12 years) and male patients over that in COSS-77 was observed in COSS-80, probably due to the increased MTX dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Amputation, Surgical↗
PubMedDate not supplied

[COALL-80 therapy in the management of acute lymphoblastic leukemia in childhood--an interim report].

In order to reduce the toxicity of the otherwise very effective childhood ALL treatment protocol BFM 76/79 asparaginase was omitted from the 4-drug induction regimen and placed as single drug before the intensification phase. In addition the effect of 3-monthly intermediate dose methotrexate (ID-MTX) pulses versus conventional vincristine (VCR) pulses during maintenance therapy was studied. Of 145 evaluable patients 124 (85.5%) survive in continuous and complete remission (CCR) at a median observation time of 21 (1,5-47) months. The expected rate of patients in CCR at 4 years is 75% respectively 80% after exclusion of 4 patients with fatal complications and one remission failure. These relapse free survival data re equal to the BFM 76/79 and 79/81 results. There was very few therapy related morbidity and no mortality from the COALL-80 induction therapy modification. The intensification phase, however, which was adopted from the BFM study without modification was difficult to manage and was not free of life threatening mostly infectious complications which were fatal in 4 cases. ID-MTX pulses did not prove superior to conventional VCR pulses. The relapse rate in patients with the c-ALL subtype was markedly lower than in any other subtype, remarkably also than in the undifferentiated type.

Adolescent↗
PubMedDate not supplied

[Chemotherapy of osteosarcoma].

Intensified adjuvant chemotherapy increased the 4-year metastasis-free survival probability from 50% (COSS-77) to roughly 80% (COSS-86). Preoperative chemotherapy was found without recognizable hazard and promoting conservative surgery. Following resection the local failure rate ist significantly higher than after demolitive procedures, including rotation plasty (10.5% vs. 2.5%). Local failures bare a very poor prognosis (19/23 DOD). The acute therapy related mortality is less than 3%. Late toxicities like ototoxicity and cardiotoxicity are intriguing and deserve increased attention. The management of the osteosarcoma patient is a complex and difficult interdisciplinary task which is best performed in centers experienced in the treatment of malignant musculo-skeletal tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Effect of a local surgical procedure on the incidence of metastases following neoadjuvant chemotherapy of osteosarcoma].

Following preoperative chemotherapy of 9-18 weeks duration limb salvage procedures were performed instead of ablative surgery in about 1/2 of the patients (pts). Overall continuous disease-free survival rate is 69% (80/115) at 37 (21-51) months. 5 pts died from therapy related complications, 4 developed a local failure (2 following amputation and 2 following limb salvage each) and 26 pts developed pulmonary metastases. The incidence of pulmonary metastases after en bloc resection, but not after shank rotation plasty, was found to be significantly increased over that after ablative surgery (83% vs 60% metastases free survival (MFS) at 40 months, p less than 0.05). The outcome was most unfavourable following en bloc resection of large tumors (36% MFS) and of tumors poorly responding to preoperative chemotherapy. Delaying surgery for preoperative chemotherapy in itself did not influence MFS-rate but it enabled a thorough planing and preparation of surgical procedures. Chemotherapy has very much improved the prognosis of osteosarcoma, trials on limb salvage surgery are indicated therefore. However, these procedures appear to be hazardous by increasing the rate of pulmonary metastases. Until the underlying mechanisms are not uncovered and preventive strategies worked out, limb salvage surgery in osteosarcoma has to be regarded and handled as an experimental procedure.

Amputation, Surgical↗
PubMedDate not supplied

[After-care of children and young adults surviving cancer. Initial recommendations by the late sequelae study group].

An increasing number of children suffering from cancer has been treated successfully during the last 25 years using therapy protocols of the Gesellschaft für Pädiatrische Onkologie und Hämatologie. The patients had to undergo an interdisciplinary treatment modality and a mostly intensive chemotherapy. Late effects could result from this approach for the now 20,000 survivors in the Federal Republik of Germany. The executive committee of the GPOH founded a working group for the detection of late effects stretching over all therapy studies. The first report of this group describes a spectrum of relevant late effects and proposes investigations for their detection.

Adolescent↗
PubMedDate not supplied

[Recommendation for studies of optimizing therapy protocols].

Guidelines to establish the principles for the standard of Good Clinical Practice (GCP) for trials on medicinal products in human beings were coming into operation in the European Community in 1991. These recommendations are more extensive than those of the German drug regulatory act (AMG). Included are outlines for the protection of the patient, the responsibilities of the investigator, for biometrics and the quality assurance. Although most of the studies in pediatric oncology optimizing treatment schedules do not belong to the studies as defined by the AMG, certain rules and regulations are strictly adhered to, e.g. the Declaration of Helsinki for the protection of human rights, medical justification of involved risks, adequate and freely obtained informed consent of the patient and the parents. Furthermore, the approval of Ethics Committees must be requested.

Child↗